Our Discoveries

Mesothelioma is a rare but aggressive form of cancer which is difficult to treat. Image credit: iStock

A rare look into what makes mesothelioma aggressive, and potentially treatable

Scientists have a limited understanding of mesothelioma and how to treat it effectively, but that’s beginning to change. In a novel study, CCR researchers identified a 48-gene signature associated with a worse prognosis – but also identified a subset of patients who respond to certain immunotherapy and chemotherapy drugs.

Lung cancer cells fluorescently labeled for MYC (red), MYCL (green) and chromosomes (blue) to identify MYC- and MYCL-positive ecDNA in the cells.

Extrachromosomal DNA promotes aggressiveness of small cell lung cancer

Cancers harboring small particles of DNA that exist outside of chromosomes, called extrachromosomal DNA (ecDNA), are associated with aggressive tumor growth, drug resistance, and shorter patient survival. New research shows that ecDNAs in small cell lung cancer contribute to variability between cancer cells, allowing them to rapidly evolve and leading to these undesirable outcomes.

Immunohistochemical staining of a human brain metastasis.

First clinical trial testing a prevention for breast cancer metastasis to the brain yields encouraging results

When breast cancer metastasizes to the brain, new tumors usually develop even after treatment. But recurrence was low among women who received low-dose temozolomide with T-DM1 in a phase I clinical trial.

Three-dimensional illustration of a SSHEL drug delivery system.

Researchers create a novel cancer drug delivery system inspired by bacterial spores

CCR researchers, led by Senior Investigator Kumaran S. Ramamurthi, Ph.D., have found a way to deliver drugs directly to cancerous tissue — at least in an animal model — by copying the structure of bacterial spores. Their synthetic, spore-like particles are a novel approach to avoiding the harmful systemic side effects of chemotherapy.

Tumor cell community in a hepatocellular carcinoma, a type of liver cancer.

Researchers uncover stable molecular networks inside liver tumors

The ever-changing nature of tumor microenvironments makes treating cancerous tumors difficult. CCR researchers, led by Xin Wei Wang, Ph.D., Deputy Chief of the Laboratory of Human Carcinogenesis, have performed single-cell RNA sequencing analyses on samples from 44 liver cancer patients. They have uncovered stable molecular networks that cells within liver tumors use to speak with nearby immune cells, which could open a path for therapeutic exploration for liver cancer.

Image credit: Marielle E. Yohe, M.D., Ph.D.

Drug Combination Shows Promise for Rhabdomyosarcoma, but Can It Get to Clinical Trials?

A study led by Marielle E. Yohe, M.D., Ph.D., Lasker Clinical Research Scholar in the Laboratory of Cell and Developmental Signaling, and Javed Khan, M.D., Deputy Chief and Senior Investigator in the Genetics Branch, has identified a potential new treatment for children with rhabdomyosarcoma. The researchers are exploring options and hope to test their drug combination in human clinical trials.

Neurons exposed to Ara-C chemotherapy trigger a DNA damage response at enhancers, marked by foci of gamma-H2AX (red) colocalizing with 53BP1 (green).

When chemotherapy interrupts genetic programs critical for neuronal development and activity, cells accrue DNA damage and die

To become neurons, brain cells must damage and immediately repair their own DNA. Some chemotherapies may harm neurons by interfering with this process.

Tumor cells are identified by islands of blue nuclei surrounded by the support cells.

Researchers exploit novel vulnerability to deprive solid tumors of nutrients

Rapidly dividing cancer cells in solid tumors can outgrow their supply of nutrients. New research suggests that tumor support cells produce collagen-derived glutamine as a source of energy for nutrient-deprived tumors. This work reveals a novel approach for designing anti-cancer drugs that can starve solid tumors.

New insights into why smoking causes fatty liver disease

A new study using nicotine-metabolizing bacteria sheds light on the cellular processes triggered by tobacco use and helps explain why smoking can lead to non-alcoholic fatty liver disease. Tobacco cessation is the best way to reduce the harmful effects of smoking. These findings could help researchers develop additional approaches to address smoking-related liver damage.

Three-dimensional illustration of a T cell attacking a cancer cell.

T-cell imbalance can impact immunotherapy outcomes

The rapid growth of a patient’s cancer following immune checkpoint inhibitor therapy, known as hyperprogressive disease, is an unexpected treatment outcome that is challenging to predict or study. New results show that a T-cell imbalance in the tumor microenvironment can trigger the condition.

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